Depression is a serious concern in the clinical management of HIV infection, affecting 20-25% of people living with HIV/AIDS (PLWHA) and predicting a range of negative HIV-related behavioral and clinical health outcomes, including greater sexual risk behavior, worse antiretroviral medication adherence, poor response to antiretroviral therapy (ART), faster immune system decline, and higher mortality. Given the strong and consistent observational associations linking depression to negative HIV-related behaviors and outcomes, do effective depression interventions improve adherence for depressed PLWHA? Standard depression treatment strategies are efficacious in PLWHA, and observational data indicate that PLWHA with treated depression have better ART adherence and clinical outcomes than those with untreated depression. A handful of small randomized controlled trials (RCTs) using psychotherapy-based depression interventions in PLWHA has tended to show improved ART adherence. Much less attention has focused on antidepressant treatment interventions, which have a greater potential than psychotherapy-based interventions to address the resource constraints and lack of psychiatric expertise that define most HIV care settings. An combination of antidepressant therapy with brief adherence counseling in a model that could be integrated into routine clinical practice settings may have great potential to improve adherence in depressed HIV patients. Our goal in this R01 proposal is to conduct an RCT of an evidence-based depression treatment intervention known as Measurement-Based Care (MBC), combined with brief Motivational Interviewing (MI) adherence counseling, in depressed PLWHA to assess its impact on ART adherence and clinical outcomes. MBC employs clinical coordinators (CCs) with expertise in depression management to screen for depression and help non-psychiatric physicians implement guideline-concordant, algorithm-driven antidepressant treatment. The CC uses standardized metrics (depressive symptoms, side effects) and an algorithm to monitor treatment response and recommend changes. Weekly supervision from a psychiatrist ensures quality care. Biweekly contact between patients and the CC will include brief MI adherence counseling. We will recruit 390 PLWHA on ART with confirmed depression, and will conduct a provider-randomized trial of the MBC intervention versus enhanced usual care. Our 3 HIV clinical sites in North Carolina have a long history of collaboration on HIV behavioral health research. Our aims are: (1) to test whether MBC improves ART adherence and HIV clinical outcomes, (2) to assess the cost-effectiveness of MBC, and (3) to collect process measures concerning MBC implementation to inform replication at other sites. Since the CC role can be effectively filled by a behavioral health provider or nurse given appropriate training and supervision and the intervention has limited time requirements, this model is potentially replicable to a wide range of resource- constrained HIV treatment settings.